Dosimetric spacer for calculating dosage administered

ABSTRACT

An apparatus for administering a fluid medicament to a patient in a gas for inhalation and for calculating the dosage administered to the patient comprising a holding member (1) for temporarily holding the medicament and gas prior to inhalation, means for introducing a quantity of the medicament into the holding chamber (1), a sensor (4) for detecting the introduction of the medicament into the holding chamber (1), detector means for detecting the rate of flow of gas inhaled by a patient from the holding chamber (1) and calculation means (25, 27, 29, 30, 31) operably connected to the sensor (4) and to the detector means for calculating the amount of medicament received by a patient. The calculating means (25, 27, 29, 30, 31) makes its calculation on the basis of the quantity of medicament released into the holding chamber (1), the volume of the holding chamber (1), the time elapsed from the detection of the introduction of the medicament, and the detected rate of flow of gas inhaled from the holding chamber (1). The calculation being made by assessing the concentration of the medicament in the holding chamber (1) on a time basis during reduction of the said concentration within the holding chamber (1), and be determining the volume of the gas received by the patient during inhalation, and the time elapsed from the detected introduction of medicament to the inhalation by the patient.

The present invention relates to a method and apparatus foradministering a measured dosage of fluid medicament to a patient in agas for inhalation.

Throughout this specification and claims reference is made to a fluidmedicament which may be a liquid or a powder in a fluidised form or inany other similar form.

Patient-operated multi-dose inhalers (MDI) are known having a mouthpiecethrough which a patient inhales. The patient must activate the MDI as hebegins to inhale so that a metered dose of medicament is sprayed into astream of air as it is sucked through the mouthpiece of the patient'sinhalation.

Unfortunately the above MDI is often operated incorrectly so that muchof the dose of medicament is wasted. The MDI must be activated or firedjust as the patient begins to inhale so that the medicament is drawndeep into the periphery of the lungs where it is most effective. If theMDI is fixed too late, most of the medicament remains in the throat orbronchial tracts without any effect. Elderly patients and children areparticularly likely to be unable to co-ordinate the firing of the MDIwith the start of inhalation.

Some MDIs and dry powder inhalers (DPI) are available which includesensors which detect when a patient is inhaling and automaticallyactivate the MDI. Whilst these MDIs and DPIs work well in detecting thecommencement of inhalation in adults, elderly patients and children havedifficulty in triggering the firing of the MDI since their inhalationflow rates are too small to be detected. Often, if a child or elderlypatient is able to activate the MDI, this only occurs once theirinhalation flow rate has increased to near its maximum, and triggeringof the MDI therefore only occurs when the lungs of the patient arealready half full.

MDIs and DPIs have been proposed which have a spacer chamber or holdingchamber in conjunction with the MDI or DPI. When the MDI is activated, adose of medicament is fired from the inhaler at high velocity. If apatient inhales the dose of medicament directly, then a large proportionof the dose will be impacted at the back of the throat due to the highvelocity. Much of the dose does not reach the lungs where the medicamentis intended to act. In some cases, less than fifty percent of the doseof medicament is deposited in the lungs. A particular problem withdirect inhalation of the medicament by children is that they are oftenunable to inhale the full dose released due to the small volume of theirlungs. The holding chamber may be disposed between the MDI and thepatient. The medicament is sprayed into the holding chamber where it isheld before the patient inhales from the holding chamber. The spacerchamber absorbs the high velocity of the medicament fired from the MDIand acts as a "buffer" chamber. The patient then inhales the dose at amuch lower velocity. This can reduce the amount of the medicamentimpacting on the back of the throat by upwards of eighty percent, andmay double the amount deposited in the lungs.

Furthermore, the use of a holding chamber means that, provided themedicament has already been fired into the holding chamber, the patientno longer needs to co-ordinate the firing with his inhalation.

The above proposal has some disadvantages. Although it is impossible toguarantee that a given dosage of medicament has actually reached deepinto the patient's lungs, it is desirable to ensure that a dose asaccurate as possible is given so that the patient's treatment is fullyeffective.

In the past, a dose of medicament has been sprayed into a holdingchamber from which the patient has repeatedly inhaled until the whole ofthe dose is presumed to have been inhaled. Such a presumption is aninaccurate measurement of dose actually inhaled by the patient. Firstly,as the patient inhales, more air is drawn into the holding chamber toreplace the air which is inhaled. This causes a dilution of themedicament within the holding chamber. Therefore, even when a patienthas inhaled two or three times, medicament remains within the holdingchamber. Secondly, the medicament sprayed into the holding chambergradually settles on the walls and base of the holding chamber overtime. This is caused in part by gravity, and in part by static chargeson the medicament and on the holding chamber. Therefore, much of themedicament is not delivered to the patient during inhalation, no matterhow many times he inhales.

It is an object of the present invention to reduce the above and otherdisadvantages, and in particular to accurately determine the dose ofmedicament received by the patient.

The scope of the present application is defined in the appended claims.

Embodiments of the present invention will now be described by way ofexample with reference to the drawings in which:

FIGS. 1 and 2 show a first embodiment of the present invention;

FIG. 3 shows how the concentration of the medicament varies over time ingraphic form;

FIG. 4 shows the variation in dilution factor as the medicament isinhaled in graphic form;

FIG. 5 shows graphically the flow through the sensor;

FIGS. 6 and 7 show a second embodiment of the present invention;

FIGS. 8, 9 and 10 show graphic characteristics of the second embodiment;

FIGS. 11 and 12 show a third embodiment of the present invention;

FIG. 13 shows a fourth embodiment of the present invention;

FIG. 14 shows graphically the flow of air or gas detected by the sensor.

FIG. 15 shows a processor circuit for calculating the dose given to thepatient, and FIG. 16 shows a further embodiment of the present inventionincluding control system.

Referring to FIG. 1 a holding chamber 1 includes an inlet 2 throughwhich a liquid medicament passes into the holding chamber from themulti-dose inhaler (MDI) 3. The MDI 3 releases the liquid medicament ina cloud of droplets. A sensor 4 is disposed between the MDI 3 and theholding chamber 1 which detects each actuation of the MDI 3. The sensor4 also detects the rate at which air or other gas enters the holdingchamber 1 via the inlet 2.

The holding chamber (also known as a spacer chamber or "buffer chamber")also includes an outlet 5 to which a mouthpiece 6 is attached. A patientinhales from the mouthpiece 6 drawing air or gas laden with medicamentfrom the holding chamber 1. This causes more air or gas to be drawn intothe holding chamber 1 through the inlet 2. The rate of flow of airthrough the inlet is detected by the sensor 4. A one way valve 7 isdisposed between the outlet 5 and the mouthpiece 6 so that the patientcan only inhale from the holding chamber 1 but cannot exhale into theholding chamber 1. The patient must remove the mouthpiece 6 from hismouth before exhaling.

Referring to FIG. 2, a second one-way valve 8 is disposed in themouthpiece 6 which permits exhaled air to be vented to atmosphere.

Once the medicament has been released into the holding chamber, theconcentration of the medicament decreases, firstly as a result ofdeposition as the medicament settles on the walls and base of theholding chamber due to gravity and electrostatic forces between thewalls of the holding chamber and the medicament. Secondly, theconcentration decreases as a result of dilution caused by air enteringthe holding chamber to replace air inhaled by the patient.

Calculations must be carried out in order to determine the dose ofmedicament which has actually been delivered to the patient. To makethese calculations, the following information must be known:

(i) the concentration of the medicament within the holding chamber 1 asshown in FIG. 3. This concentration depends on the number of actuationsof the MDI releasing the medicament into the holding chamber and on theamount of time between the release of the medicament into the holdingchamber and the patient inhaling since the medicament sediments overtime; and

(ii) the dilution factor where the concentration of the medicament inthe holding chamber 1 decreases each time the patient inhales since airor gas not containing medicament enters the holding chamber 1. Thisdilution is shown in FIG. 4.

From this information, the dose of medicament received by the patient ismonitored, and an indication is given by the apparatus when the desireddose has been administered.

This indication may be audible or visual.

Referring to FIG. 5 the detected flow pattern through the inlet 2 of theholding chamber 1 is shown. Treatment starts upon firing of the MDIwhereafter the inhalation of the patient is detected. The rate ofinhalation is detected so that the calculations may be made to determineat what point the desired dose has been given. This point can then beindicated.

Calculation of the dose given to the patient shall now be described inconnection with the embodiment shown in FIG. 2. The patient firstlyconnects the MDI 3 to the inlet port 2. The MDI 3 is fired to release acloud of medicament into the holding chamber 1 past the sensor 4. Thesensor 4, which might be a microphone or a pressure detector, detectsthe introduction of medicament into the holding chamber 1 and produces asignal. A data processor (not shown) receives the signal from the sensor4 and starts a clock (not shown). The patient then puts the mouthpiece 6to his mouth and inhales. Air and medicament within the holding chamberis drawn from the holding chamber through the port 5 and the mouthpiece.At the same time, air enters the holding chamber 1 through port 2 toreplace the inhaled air, thereby causing dilution. The data processorcalculates the amount of medicament delivered to the patient at veryfrequent intervals, typically every one hundredth of a second. In eachof these sampled periods, the concentration of medicament within theholding chamber 1 is calculated to take account of the deposition of themedicament on the walls of the holding chamber 1 over time, and of thedilution effect of air entering the holding chamber 1 which does notcarry any medicament. A memory contains a data look-up table which givesthe concentration of medicament in the chamber at a time after theintroduction of the medicament based on the deposition rate of themedicament. The memory also contains a data look-up table which givesthe concentration of medicament in the chamber following theintroduction of a set volume of air. The concentration of medicamentwithin the holding chamber 1 is therefore calculated at the sampledtime. The dose of medicament inhaled is then calculated by multiplyingthe volume of air sensed by the sensor during the sampled period by theconcentration of medicament within the holding chamber at that sampledperiod. The dose calculated during this one sample period is then addedto the dose calculated in calculations for previous sample periods. Oncethe cumulative total dose reaches a predetermined level, an indicationis made to the patient that the full dose has been given. This might beindicated by a light or by an audible signal. The patient may requireseveral breaths before the predetermined dose has been inhaled. Thepatient is able to exhale between inhalations through the mouthpiecesince the one way valve 8 is able to vent the exhaled air to atmosphere.

The microprocessor must also count the number of actuations or firingsof the MDI in order to calculate the initial concentration of medicamentwithin the holding chamber 1. The calculation apparatus used in thisembodiment is similar to the calculation apparatus described later inthis specification in connection with FIGS. 15 and 16. However, in thepresent embodiment, in addition to the decrease in concentration causedby deposition of the medicament, the dilution must also be taken intoaccount.

Referring now to FIG. 6, an alternative apparatus is shown whichoperates in conjunction with dry powder inhalers (DPI). DPIs arenormally actuated by the patient's inspiratory flow. They are notsuitable for patients with a very low inspiratory flow since the DPI isunlikely to be triggered reliably. Dry powder inhalers release themedicament in the form of a fine powder which is inhaled by a patientinto their lungs. As with conventional MDIs, conventional DPIs sufferfrom the disadvantage that much of a given dose impacts with the back ofa patient's throat. Referring to FIG. 6, a holding chamber 1 includes afirst port 9 which is used both to load and empty the holding chamber 1.The holding chamber also includes a piston 10 movable within thechamber 1. As the piston 10 is drawn back, air or gas is sucked into theholding chamber 1 via the first port 9, and air trapped behind thepiston escapes through a second port 11.

The holding chamber 1 includes a one way valve 12 which communicateswith the gas or air loaded with medicament only when the piston 10 ispulled fully back. The one-way valve 12 permits air only to enter thebuffer chamber.

In use, the piston 10 is pulled back drawing air or gas into the holdingchamber 1 through the first port 9. Before reaching the first port 9,the air or gas passes through a dry powder inhaler 13 which releases themedicament into the air or gas, and through a sensor 4. Once the piston10 has been pulled back fully, it reveals the one-way valve 12. Thepiston 10 is fired in that position. The patient then removes the DPI 13and replaces it with a mouthpiece 6 as shown in FIG. 7. The patient theninhales from the mouthpiece 6 and air or gas loaded with the medicamentis sucked from the holding chamber passing through the port 9, throughthe sensor 4 and through the mouthpiece 6. The sensor 4 detects thisairflow as shown in FIG. 10. Ambient air enters the buffer or holdingchamber 1 through the one-way valve 12 in order to replace the air orgas being inhaled.

Calculations can again be made to accurately measure when a given doseof medicament has been administered. Again, it is necessary to know theconcentration of the medicament within the holding chamber 1, as shownin FIG. 8, since sedimentation of medicament occurs over time. It isalso necessary to know the dilution factor during inhalation as shown inFIG. 9. These can be calculated from the output of the sensor 4 asdescribed in connection with FIG. 2.

Once the correct dose has been administered, this is indicated. Afurther embodiment is shown in FIGS. 11 and 12 and, in this embodimentthe piston 10 returns across the holding chamber 1 as the patientinhales. There is no one-way valve 12 in the holding chamber as in theprevious embodiment. During inhalation and, consequently, emptying ofthe holding chamber 1, the piston is arranged to move only in thedirection of emptying the holding chamber 1 to prevent dilution. Topermit the patient to exhale, a one-way valve 14 is disposed in themouthpiece 6.

Another advantage of this embodiment is that the dilution factor iseliminated, making dosage calculations simper, quicker and moreaccurate. No air enters the holding chamber 1 to replace the air or gasbeing inhaled since the piston moves to replace the inhaled air.

Calculation of the dose given to the patient shall now be described inconnection with the embodiment shown in FIGS. 11 and 12. The patientfirstly connects the DPI 13 to the port 9. The piston 10 is pulled backdrawing air into the holding chamber 1 via the DPI 13 and the port 9.The sensor 4, which might be a microphone or a pressure detector,detects this introduction of medicament into the holding chamber 1 andproducts a signal. A data processor (not shown) receives the signal fromthe sensor 4 and starts a clock (not shown). The patient then removesthe DPI from the port 9 and replaces it with a mouthpiece (FIG. 12). Thepatient inhales through the mouthpiece, and the air flows past thesensor 4. The data processor calculates the amount of medicamentdelivered to the patient very frequently, typically every one hundredthof a second. The concentration of medicament within the holding chamber1 is continuously calculated to take account of the deposition ofmedicament on the walls of the holding chamber 1 over time. A memorycontains a data look-up table which gives the concentration ofmedicament in the chamber 1 at a time after introduction of themedicament. The dose of medicament inhaled is then calculated bymultiplying the volume of air sensed by the sensor by the concentrationof medicament. The dose calculated during this one hundredth of a secondsample period is then added to the dose calculated in calculations forprevious sample periods. Once the cumulative total dose reaches apredetermined level, an indication is made to the patient that the fulldose has been given. This might be indicated by a light or by an audiblesignal.

FIG. 15 shows a block diagram of the processor system including aprocessor 25 powered by a power supply 34. The sensor 4 sends signals tothe processor 25 via an amplifier 32 to indicate when the medicament isbeing introduced into the holding chamber 1, and the rate of inhalationof the patient. The processor 25 calculates the dose given to thepatient on the basis of a program 29, a memory 30 containing look-updata 31, and a clock 27 and analog to digital converter (A/D) 28. Oncethe processor has calculated that the predetermined dose has been given,a signal is output via the data output 33.

Referring to FIGS. 13 and 14, the whole system may be controlled bymovement of the piston 10. No valves are used, but the mouthpiece 6includes two inlets, one from atmosphere and the other from the holdingchamber 1. The sensor 4 detects when the patient is inhaling andexhaling. The piston 10 is automatically moved forwards when the patientinhales so that the patient inhales the air or gas containing medicamentfrom the holding chamber 1. As with the earlier embodiments, an audibleor visual warning can be given when the patient has received the correctdose.

In such an embodiment, once the piston has been withdrawn to fill theholding chamber 1 with medicament and air, biassing means may be used tobiase the piston to push the air and medicament out of the holdingchamber 1, and locking means for fixing the piston. The sensor 4 is apressure sensor which senses the commencement of inhalation by apatient, and the microprocessor 25 releases the locking means to enablethe piston to move through the holding chamber 1 in order to dispensesufficient air and medicament to satisfy the inhalation of the patient,before the locking means fixes the piston once the sensor 4 detects thatthe patient stopped inhaling. When the patient exhales, the exhaledbreath is vented through the one way valve 14 in the mouthpiece. Theinhalation process is repeated until the microprocessor determines thatthe predetermined dose has been administered at which point the patientis warned, and the locking means permanently fixes the piston so that nofurther medicament can be inhaled from the holding chamber 1. In afurther embodiment, as shown in FIG. 16, a piston 10 is movable througha holding chamber 1 having a port 9 through which air and medicament isdrawn from a DPI as the piston 10 is withdrawn. The piston 10 iswithdrawn by a patient pulling a connecting rod 20. The connecting rod20 is toothed, and a solenoid latch 21 is disposed just outside theholding chamber 1 which is engageable with the toothed connecting rod 20to lock the piston 10. An optional spring 22 is disposed around theconnecting rod 20 between the piston 10 and one end of the holdingchamber 1 which biases the piston 10 to expel gas and medicament fromthe holding chamber 1. Furthermore, a dose panel 35 is included forindicating the proportion of the prescribed dose which has beenadministered. This embodiment operates in generally the same way asdescribed above in connection with FIGS. 11, 12 and 15 in that the dosegiven to the patient is continuously monitored. The processor 25 usesthe signal from the sensor 4, a clock signal from a clock 27, data onpredetermined dose 40 and data 31 on how the concentration varies withtime in the form of a look-up table. As the calculated dose given to thepatient increases, LEDs on the dose panel 35 are illuminatedcorresponding to the proportion of the predetermined dose given, in thiscase a new LED is illuminated on each of 25%, 50%, 75% and 100%.Further, when the full predetermined dose has been administered, themicroprocessor 25 drives the solenoid latch 21 to engage with thetoothed connecting rod 20 to lock the piston 10. This prevents anyfurther medicament being delivered to the patient. The microprocessorsystem also includes a compliance data memory 36 for recording the date,time and dose delivered which can subsequently be analyzed by a doctor.

Reference has been made above to look up tables which give data on howconcentration of medicament decreases in time, and how concentration ofmedicament decreases by dilution caused by inhalation of known volumes.The data in the look-up tables must be gathered by experiment. Forexample, when the data for decrease in concentration of medicament withtime is gathered, a known amount of medicament is introduced into theholding chamber, and the air in the holding chamber 1 is then expelledafter a time into a filter paper. The expelled medicament is thenweighed. This experiment is repeated for different time periods toestablish the necessary data. The variation of concentration with timeprofile is likely to be different for different medicaments. Thereforethe apparatus must have the correct profile programmed in.

The data of decrease in concentration of medicament with dilution iscollected by introducing a known amount of medicament into the holdingchamber, diluting the medicament by replacing some of the air, and thenexpelling the air and medicament into a filter paper. A profile can thenbe created.

In general, the holding chamber 1 would typically be of the order of100-500 ml in volume, and the sensor 4 might be of the pressure type,such as a pneumatic, or of the turbulence-detecting type such as amicrophone.

We claim:
 1. Apparatus for administering a fluid medicament to a patientin a gas for inhalation and for calculating the dosage administered tothe patient comprisinga holding chamber for temporarily holding themedicament and gas prior to inhalation; means for introducing a quantityof the medicament into the holding chamber; a sensor for sensing theintroduction of the medicament into the holding chamber; detector meansfor detecting the rate of flow of gas inhaled by a patient from theholding chamber; and calculation means operably connected to the sensorand to the detector means for calculating the amount of medicamentreceived by a patient on the basis of:the preset quantity of medicamentreleased into the holding chamber; of the preset volume of the holdingchamber; the time elapsed from the sensing of the introduction of themedicament; and of the detected rate of flow of gas inhaled from theholding chamber; the calculation being made by assessing theconcentration of the medicament in the holding chamber on a time basisduring reduction of the said concentration within the holding chamberdue at least in part to deposition of the medicament within the holdingchamber, and by determining the volume of the gas received by thepatient during inhalation, and the time elapsed from the sensedintroduction of medicament to the inhalation by the patient. 2.Apparatus according to claim 1 including indication means for indicatingthat the measured dosage has been administered.
 3. Apparatus foradministering a fluid medicament to a patient in a gas for inhalationand for calculating the dosage administered to the patient comprisingaholding chamber for holding the medicament and gas prior to inhalation;means for introducing a quantity of the medicament into the holdingchamber; a sensor for sensing introduction of the medicament into theholding chamber; detector means for detecting the rate of flow of gasinhaled by a patient from the holding chamber; and calculation meansoperably connected to the sensor and to the detector means forcalculating the amount of medicament received by a patient, thecalculation means includinga timing means for indicating the timeelapsed since the sensor senses the introduction of medicament into theholding chamber; means for supplying the initial concentration ofmedicament in the holding chamber immediately after the introduction ofmedicament therein; means for determining the concentration ofmedicament in the holding chamber during inhalation by the patient, theconcentration of medicament reducing with time due at least in part todeposition of the medicament within the holding chamber, thedetermination being made on the basis of the initial concentrationsupplied by the means for supplying initial concentration, and of thetime elapsed since the sensor sensed the introduction of medicament intothe holding chamber; and means for determining the amount of medicamentreceived by the patient by calculating the volume of gas inhaled by thepatient from the holding chamber by integrating the rate of flowdetected by the detector means, and by multiplying the calculated volumeof gas by the concentration of medicament in the holding chamber at thattime determined by the means for determining the concentration ofmedicament.
 4. Apparatus according to claim 3 including a memory forstoring a look-up chart showing the decrease of concentration of themedicament in the holding chamber over time.
 5. Apparatus according toclaim 4 wherein the means for determining the concentration ofmedicament in the holding chamber during inhalation makes the saiddetermination also on the basis of the look-up chart in the memory. 6.Apparatus according to claim 3 wherein the means for supplying initialconcentration of medicament in the holding chamber immediately after theintroduction of medicament determines the said initial concentration onthe basis of a preset quantity of medicament introduction into theholding chamber, and of a preset volume of the holding chamber. 7.Apparatus according to claim 3 wherein the holding chamber includes aninlet for permitting entry of gas into the holding chamber as gas isdrawn out of the holding chamber by inhalation thereby causing areduction of the concentration of medicament within the holding chamberby dilution.
 8. Apparatus according to claim 7 wherein the means fordetermining the concentration of medicament in the holding chamberduring inhalation makes the said determination also on the basis of thevolume of gas previously inhaled by the patient.
 9. Apparatus accordingto claim 7 including a memory for storing a look-up chart showing thedecrease of concentration of the medicament in the holding chamber withthe volume of air inhaled.
 10. Apparatus according to claim 3 whereinthe holding chamber includes a piston for reducing the volume of gas inthe holding chamber as gas is inhaled, thereby preventing dilution. 11.Apparatus according to claim 10 including means for locking the piston.12. Apparatus according to claim 11 wherein the means for locking thepiston locks the piston upon administration of the measured dose. 13.Apparatus according to claim 10 wherein the piston is movable within theholding chamber for drawing gas and medicament into the holding chamber.14. Apparatus according to claim 3 including a port in the holdingchamber through which a quantity of medicament is introduced into theholding chamber by said releasing means, and through which gas isinhaled by a patient.
 15. Apparatus according to claim 3 wherein themedicament is a cloud of liquid droplets.
 16. Apparatus according toclaim 3 wherein the medicament is a cloud of dry powder particles. 17.Apparatus according to claim 3 wherein the holding chamber includes aport through which the gas disposed in the chamber is inhaled, andthrough which the medicament is released into the holding chamber. 18.Apparatus according to claim 3 wherein the sensor for sensingintroduction of medicament into the holding chamber and the detectormeans for detecting the rate of flow of gas inhaled by a patient fromthe holding chamber are constituted by a single sensor.
 19. Apparatusaccording to claim 18 wherein the single sensor is disposed in the portof the holding chamber.
 20. Apparatus for administering a fluidmedicament to a patient in a gas for inhalation and for calculating thedosage administered to the patient comprisinga holding chamber fortemporarily holding the medicament and gas prior to inhalation; meansfor introducing a quantity of the medicament into the holding chamber; asensor for sensing the introduction of the medicament into the holdingchamber; detector means for detecting the rate of flow of gas inhaled bya patient from the holding chamber; and calculation means operablyconnected to the sensor and to the detector means for calculating theamount of medicament received by a patient on the basis of:the presetquantity of medicament released into the holding chamber; of the presetvolume of the holding chamber; the time elapsed from the sensing of theintroduction of the medicament, of the detected rate of flow of gasinhaled from the holding chamber; the calculation being made byassessing the concentration of the medicament in the holding chamber onthe basis of the detected inhaled volume during reduction of the saidconcentration within the holding chamber due at least in part todilution of the medicament within the holding chamber, and bydetermining the volume of the gas received by the patient duringinhalation.
 21. Apparatus for administering a fluid medicament to apatient in a gas for inhalation and for calculating the dosageadministered to the patient comprisinga holding chamber for holding themedicament and gas prior to inhalation; means for introducing a quantityof the medicament into the holding chamber; a sensor for sensingintroduction of the medicament into the holding chamber; detector meansfor detecting the rate of flow of gas inhaled by a patient from theholding chamber; and calculation means operably connected to the sensorand to the detector means for calculating the amount of medicamentreceived by a patient, the calculation means includinga timing means forindicating the time elapsed since the sensor senses the introduction ofmedicament into the holding chamber; means for supplying the initialconcentration of medicament into the holding chamber immediately afterthe introduction of medicament therein; means for determining theconcentration of medicament in the holding chamber during inhalation bythe patient, the concentration of medicament reducing with the volume ofgas inhaled due at least in part to dilution of the medicament withinthe holding chamber, the determination being made on the basis of theinitial concentration supplied by the means for supplying initialconcentration, and of the volume of gas inhaled, calculated from therate of flow of gas detected by the detector since the sensor sensed theintroduction of medicament into the holding chamber; and means fordetermining the amount of medicament received by the patient bycalculating the volume of gas inhaled by the patient from the holdingchamber by integrating the rate of flow detected by the detector means,and by multiplying the calculated volume of gas by the concentration ofmedicament in the holding chamber at that time determined by the meansfor determining the concentration of medicament.
 22. A method foradministering a measured dosage of a fluid medicament to a patient in agas for inhalation using an apparatus comprising:a holding chamber forholding the medicament and gas prior to inhalation; means forintroducing a quantity of medicament into the holding chamber; a sensorfor sensing the introduction of medicament into the holding chamber;detector means for detecting the rate of flow of gas inhaled by apatient from the holding chamber; and calculation means operablyconnected to the sensor and to the detector means for calculating theamount of medicament received by a patient; the methodcomprising:sensing the introduction of medicament into the holdingchamber, the sensing being made by the sensor; monitoring the timeelapsed since the introduction of the medicament is sensed, themonitoring being made by the calculation means; supplying the value ofthe initial concentration of medicament in the holding chamber;determining the concentration of medicament in the holding chamberduring inhalation by the patient, the concentration of medicamentreducing with time due at least in part to deposition of the medicamentwithin the holding chamber, the determination being made on the basis ofthe supplied initial concentration and of the time elapsed since thesensor senses the introduction of medicament into the holding chamber;and determining the amount of medicament received by the patient bycalculating the volume of gas inhaled by the patient from the holdingchamber by integration of the rate of flow detected by the detectormeans, and by multiplying the calculated volume of gas by the determinedconcentration of medicament in the holding chamber at that time.
 23. Amethod of administering a fluid medicament to a patient in a gas forinhalation and for calculating the dosage administered to the patientcomprisingsensing the introduction of a quantity of medicament into aholding chamber; detecting the rate of flow of gas inhaled by a patientfrom the holding chamber; monitoring the time elapsed from the sensingof the introduction of the quantity of medicament into the holdingchamber; determining the concentration of medicament in the holdingchamber during inhalation by the patient, the concentration ofmedicament reducing with time due at least in part to deposition of themedicament within the holding chamber, the determination being made onthe basis of the predetermined initial concentration of medicamentwithin the holding chamber immediately after the introduction ofmedicament therein, and on the basis of the monitored time elapsed sincethe sensing of the introduction of medicament; and calculating theamount of medicament received by the patient by calculating the volumeof gas inhaled by the patient from the holding chamber by integratingthe detected rate of flow, and by multiplying the calculated volume ofgas inhaled by the determined concentration of medicament in the holdingchamber.